Study results of topical PDT for non melanoma skin cancer
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6090",leadTitle:null,fullTitle:"Aspects in Dialysis",title:"Aspects in Dialysis",subtitle:null,reviewType:"peer-reviewed",abstract:"Dialysis (clearance of uremic toxins and removal of excess fluids) is a broad term for different modalities of treatment for patients with acute and end-stage kidney disease. These modalities include peritoneal dialysis, hemodialysis, hemofiltration, hemodiafiltration, and continuous renal replacement therapy for critically ill patients with acute kidney injury. Dialysis is a lifesaving measure and can be conducted in hospitals, in dialysis clinics, and at home. Recently, dialysis techniques have witnessed tremendous improvements in technology and performance. The book Aspects in Dialysis covers important aspects of dialysis-related topics and is empowered with well-established and experienced authors, who have written clear and informative chapters. It covers various aspects of dialysis modalities supported by well-established clinical studies. Aspects in Dialysis can be considered as a guide for daily practice and a reference for medical and nursing staff involved in taking care of dialysis patients.",isbn:"978-1-78923-025-3",printIsbn:"978-1-78923-024-6",pdfIsbn:"978-1-83881-285-0",doi:"10.5772/68136",price:119,priceEur:129,priceUsd:155,slug:"aspects-in-dialysis",numberOfPages:174,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"be78832ec657b137d473accee9fe221d",bookSignature:"Ayman Karkar",publishedDate:"April 25th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6090.jpg",numberOfDownloads:7279,numberOfWosCitations:0,numberOfCrossrefCitations:2,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:4,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:6,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 7th 2017",dateEndSecondStepPublish:"March 28th 2017",dateEndThirdStepPublish:"November 19th 2017",dateEndFourthStepPublish:"December 19th 2017",dateEndFifthStepPublish:"February 19th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"156627",title:"Dr.",name:"Ayman",middleName:null,surname:"Karkar",slug:"ayman-karkar",fullName:"Ayman Karkar",profilePictureURL:"https://mts.intechopen.com/storage/users/156627/images/system/156627.jpeg",biography:"Following his graduation from medical school, Dr. Ayman Karkar received his MSc degree in Nephrology and Hypertension and his PhD degree in Renal Medicine from Hammersmith Hospital, University of London. Dr. Karkar is a consultant physician and nephrologist, Fellow of the Royal Colleges of Physicians of London, Edinburgh, Glasgow, and Ireland, and Fellow of the American National Kidney Foundation and the American Society of Nephrology. He has authored several books and book chapters and published over 150 articles and abstracts in peer-reviewed medical journals. Dr. Karkar is currently Baxter Head of Medical Affairs—Renal Care, Middle East and Africa, and Subject Matter Expert, East and Central Europe and Middle East and Africa.",institutionString:null,position:null,outsideEditionCount:null,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"3",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1163",title:"Nephrology",slug:"nephrology"}],chapters:[{id:"59983",title:"Introductory Chapter",doi:"10.5772/intechopen.74849",slug:"introductory-chapter-2018-04-17",totalDownloads:773,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Ayman Karkar",downloadPdfUrl:"/chapter/pdf-download/59983",previewPdfUrl:"/chapter/pdf-preview/59983",authors:[{id:"156627",title:"Dr.",name:"Ayman",surname:"Karkar",slug:"ayman-karkar",fullName:"Ayman Karkar"}],corrections:null},{id:"56795",title:"Uremic Retention Solutes",doi:"10.5772/intechopen.70461",slug:"uremic-retention-solutes",totalDownloads:876,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter will address the broad subject of uremic retention solutes (URS), also known as uremic toxins. Some of these solutes had been recognized for decades, and in 1999 when the European Uremic Toxin Work Group was established, a fuller description of URS was presented. The group sought to identify and characterize the solutes in the serum of patients with impaired glomerular filtration, in order to explore their role in the pathogenesis of the uremic syndrome and improve current therapeutic options. This chapter will review the different types of URS, as well as the adverse effects associated with their accumulation. It will also cover current and potential therapeutic approaches to reduce their levels.",signatures:"William Ackley, Leland Soiefer, Aleksey Etinger and Jerome\nLowenstein",downloadPdfUrl:"/chapter/pdf-download/56795",previewPdfUrl:"/chapter/pdf-preview/56795",authors:[{id:"206403",title:"Prof.",name:"Jerome",surname:"Lowenstein",slug:"jerome-lowenstein",fullName:"Jerome Lowenstein"},{id:"206605",title:"Dr.",name:"Aleksey",surname:"Etinger",slug:"aleksey-etinger",fullName:"Aleksey Etinger"},{id:"207148",title:"Dr.",name:"William",surname:"Ackley",slug:"william-ackley",fullName:"William Ackley"},{id:"207149",title:"Mr.",name:"Leland",surname:"Soiefer",slug:"leland-soiefer",fullName:"Leland Soiefer"}],corrections:null},{id:"56660",title:"Body Composition and Its Clinical Outcome in Maintenance Hemodialysis Patients",doi:"10.5772/intechopen.70353",slug:"body-composition-and-its-clinical-outcome-in-maintenance-hemodialysis-patients",totalDownloads:1238,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Previous epidemiological cohorts demonstrated that higher body mass index (BMI) was associated with greater survival in patients treated by hemodialysis. Although BMI is a simple measure of adiposity in general population, it may be an inaccurate indicator of nutritional status, particularly among dialysis patients given that it does not differentiate between muscle mass and fat as well as body fat distribution. This problem might be aggravated in end-stage renal disease patients because of wasting or edema. In addition, individuals with higher BMI usually have both higher muscle and fat mass than those with lower BMI. Therefore, more sophisticated tool of body composition analysis is needed to address the query of which component is associated with mortality outcome among patients receiving hemodialysis. We summarized the current state of body composition, including lean and fat tissue evaluated by bioelectrical impedance analysis, dual X-ray absorptiometry, computerized tomography, or magnetic resonance imaging, and its association with clinical outcomes among hemodialysis patients. The studies using anthropometry for the estimation of muscle mass, either mid-arm muscle circumference as a proxy of muscle mass or skinfold thickness and waist circumference as a surrogate of body fat and visceral fat, respectively, were all included in this review.",signatures:"Piyawan Kittiskulnam and Somchai Eiam-Ong",downloadPdfUrl:"/chapter/pdf-download/56660",previewPdfUrl:"/chapter/pdf-preview/56660",authors:[{id:"49591",title:"Dr.",name:"Somchai",surname:"Eiam-Ong",slug:"somchai-eiam-ong",fullName:"Somchai Eiam-Ong"},{id:"207411",title:"Dr.",name:"Piyawan",surname:"Kittiskulnam",slug:"piyawan-kittiskulnam",fullName:"Piyawan Kittiskulnam"}],corrections:null},{id:"56689",title:"Cardiovascular Disease in Dialysis Patients",doi:"10.5772/intechopen.70362",slug:"cardiovascular-disease-in-dialysis-patients",totalDownloads:1080,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cardiovascular disease (CVD) is highly prevalent in the dialysis population, affecting up to 60% of cohorts. Cardiovascular mortality rates are reported to be ~14 per 100 patient-years, which are 10- to 20-fold greater than those of age- and gender-matched controls. CVD is the primary cause of death in up to 40% of dialysis patients in Australia, New Zealand and the United States. Dialysis patients endure a greater burden of both traditional risk factors for CVD and risk factors related to loss of kidney function that may account for the higher CVD morbidity and mortality. Many cardiology guidelines include chronic kidney disease (CKD) and end-stage kidney disease (ESKD) as coronary heart disease (CHD) risk equivalents. It is therefore important for clinicians to both recognise and optimise the cardiovascular health of patients receiving maintenance dialysis. This chapter will focus on risk factor modification, screening and prevention of CVD in dialysis patients.",signatures:"Dev Jegatheesan, Wenling Yang, Rathika Krishnasamy, Carmel M.\nHawley and David W. Johnson",downloadPdfUrl:"/chapter/pdf-download/56689",previewPdfUrl:"/chapter/pdf-preview/56689",authors:[{id:"50425",title:"Prof.",name:"David",surname:"Johnson",slug:"david-johnson",fullName:"David Johnson"},{id:"172329",title:"Dr.",name:"Carmel",surname:"Hawley",slug:"carmel-hawley",fullName:"Carmel Hawley"},{id:"207209",title:"Dr.",name:"Dev",surname:"Jegatheesan",slug:"dev-jegatheesan",fullName:"Dev Jegatheesan"},{id:"207210",title:"Dr.",name:"Wenling",surname:"Yang",slug:"wenling-yang",fullName:"Wenling Yang"},{id:"215314",title:"Dr.",name:"Rathika",surname:"Krishnasamy",slug:"rathika-krishnasamy",fullName:"Rathika Krishnasamy"}],corrections:null},{id:"56739",title:"High-efficiency Hemodiafiltration",doi:"10.5772/intechopen.70441",slug:"high-efficiency-hemodiafiltration",totalDownloads:1030,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The high mortality of hemodialysis (HD) patients is partly due to the limited capacity of diffusion-based HD to remove large uremic toxins. Hemodiafiltration (HDF) which combines convection with diffusion could enhance both large and protein-bound uremic toxin removal. Recently, there have been several randomized controlled trials demonstrating that high-efficiency post-dilution online HDF could improve survival. Indeed, high blood flow rate, which is the necessary requirement, could not be achieved in some patients. The alternative HDF techniques that could provide comparative efficacy would be considered. Pre-dilution online HDF could be performed without risk of hemoconcentration. Mid-dilution online HDF could be conducted via either simple way by using two dialyzers with the substitution fluid line in between or using special designed dialyzer. Mixed-dilution online HDF requires additional substitution pump for both pre- and post-dilution. There are interesting HDF techniques that could be performed with the conventional HD machine and these include HD with double high-flux, enhanced internal filtration, or super high-flux dialyzers. These modalities enhance the convective clearance in combination with internal backfiltration within the dialyzer in HD platform. All of these alternative high-efficiency HDF modalities are available and can potentially provide quite equivalent benefits with the high-efficiency post-dilution online HDF.",signatures:"Khajohn Tiranathanagul and Somchai Eiam-Ong",downloadPdfUrl:"/chapter/pdf-download/56739",previewPdfUrl:"/chapter/pdf-preview/56739",authors:[{id:"49591",title:"Dr.",name:"Somchai",surname:"Eiam-Ong",slug:"somchai-eiam-ong",fullName:"Somchai Eiam-Ong"},{id:"207817",title:"Associate Prof.",name:"Khajohn",surname:"Tiranathanagul",slug:"khajohn-tiranathanagul",fullName:"Khajohn Tiranathanagul"}],corrections:null},{id:"56865",title:"Cardiovascular Risk Factors in End-Stage Renal Disease Patients: The Impact of Conventional Dialysis versus Online-Hemodiafiltration",doi:"10.5772/intechopen.70465",slug:"cardiovascular-risk-factors-in-end-stage-renal-disease-patients-the-impact-of-conventional-dialysis-",totalDownloads:1415,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"End-stage renal disease (ESRD) patients present high incidence of cardiovascular (CV) events, which are the most common causes of death in these patients. The occurrence of CV events appears as a consequence of the high prevalence of traditional and non-traditional CV risk factors. Online-hemodiafiltration (OL-HDF) was introduced as a better alternative to conventional dialysis, as it was proposed to be more biocompatible, to increase dialysis efficacy, to reduce the inflammatory response to treatment and to improve patient’s quality of life, contributing to reduce CV and all-cause mortality risk in ESRD. However, data in literature, comparing the effect of OL-HDF with conventional dialysis for clinical CV outcome and all-cause mortality, yielded controversy about those benefits of OL-HFD over standard hemodialysis. A review of the traditional CV risk factors (e.g., arterial hypertension, diabetes mellitus, dyslipidemia, obesity, smoking and advanced age), non-traditional risk factors (e.g., anemia, oxidative stress, hyperphosphatemia, endothelial dysfunction, left ventricular hypertrophy, insulin resistance, high levels of lipoprotein(a) and inflammation) and potential renocardiovascular biomarkers, in the setting of ESRD, is presented. The impact of conventional hemodialysis and OL-HDF on CV risk factors and on the outcome of ESRD patients is also addressed.",signatures:"Susana Coimbra, Maria do Sameiro Faria, Vasco Miranda, Luís Belo\nand Alice Santos-Silva",downloadPdfUrl:"/chapter/pdf-download/56865",previewPdfUrl:"/chapter/pdf-preview/56865",authors:[{id:"56250",title:"Prof.",name:"Luís",surname:"Belo",slug:"luis-belo",fullName:"Luís Belo"},{id:"56251",title:"Prof.",name:"Alice",surname:"Santos Silva",slug:"alice-santos-silva",fullName:"Alice Santos Silva"},{id:"66774",title:"Prof.",name:"Susana",surname:"Coimbra",slug:"susana-coimbra",fullName:"Susana Coimbra"},{id:"215847",title:"Dr.",name:"Maria Do Sameiro",surname:"Faria",slug:"maria-do-sameiro-faria",fullName:"Maria Do Sameiro Faria"},{id:"215848",title:"Dr.",name:"Vasco",surname:"Miranda",slug:"vasco-miranda",fullName:"Vasco Miranda"}],corrections:null},{id:"59949",title:"Angiogenesis and Lymphangiogenesis in Peritoneal Dialysis",doi:"10.5772/intechopen.74015",slug:"angiogenesis-and-lymphangiogenesis-in-peritoneal-dialysis",totalDownloads:868,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The ultrafiltration failure during peritoneal dialysis (PD) is related to inflammatory responses induced by bio-incompatible PD fluids, which may lead to deterioration of peritoneal membrane (PM) function. Mesothelial cells, lymphocytes, macrophages and other cell types present in the peritoneal cavity are stimulated to produce cytokines and growth factors that promote pathological processes. Due to these factors, blood and lymphatic vessels proliferate and could be responsible for hyperfiltration and PM failure type III and IV. Vessels proliferation may be related to fibrosis, being the cause and/or effect of the mesenchymal conversion of different cell types such as mesothelial (MMT), bone marrow-derived (fibrocytes) or endothelial (vascular- and lymph-endo-MT) cells. Lymphangiogenesis in PD is a poorly analysed process; however, its contribution to peritoneal function disorders has been recently recognized. VEGF production is associated with blood and lymphatic vessels proliferation, while specifically lymphangiogenesis is mainly regulated by VEGF-C and VEGF-D. Excessive lymphatic fluid drainage from the abdominal cavity may be related with macromolecule and isosmotic solutions reuptake and convective reabsorption of solutes that were cleared from plasma by diffusion. Some drugs have been shown to modulate tissue fibrosis, MMT, EndoMT, angiogenesis and lymphangiogenesis and could represent interesting therapeutic strategies to protect the PM.",signatures:"Guadalupe Tirma Gónzalez-Mateo, Lucía Pascual-Antón, Lorena\nÁvila Carrasco, Virginia Martínez-Cabeza, Inmaculada Fernández,\nRafael Selgas, Manuel López-Cabrera and Abelardo Aguilera",downloadPdfUrl:"/chapter/pdf-download/59949",previewPdfUrl:"/chapter/pdf-preview/59949",authors:[{id:"159084",title:"Dr.",name:"Abelardo",surname:"Aguilera Peralta",slug:"abelardo-aguilera-peralta",fullName:"Abelardo Aguilera Peralta"},{id:"189211",title:"Mr.",name:"Manuel",surname:"López Cabrera",slug:"manuel-lopez-cabrera",fullName:"Manuel López Cabrera"},{id:"211999",title:"Ph.D.",name:"Guadalupe Tirma",surname:"González-Mateo",slug:"guadalupe-tirma-gonzalez-mateo",fullName:"Guadalupe Tirma González-Mateo"},{id:"237821",title:"Ph.D. 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\r\n\tRisk management aims to develop an efficient organizational development environment through risk planning, assessment, analysis, and control. This process will apply in all areas of activity, and the evaluation framework is the same regardless of the field. This volume will aim to appeal to chapters that address methods, models, evaluation frameworks, benefits, barriers, and other dimensions of risk management.
\r\n\tSustainability and the circular economy are approaches approached by many companies and have become activities of global interest. Protecting the environment, streamlining the consumption of organizational resources, reducing the amount of waste generated, and other activities are objectives of these efforts. The circular economy contributes to the sustainable development of the company or country and the achievement of the global objectives of sustainable development. This book will aim to collect various studies for organizational and global sustainability.
\r\n\tLeadership has become a globally desirable approach that can help improve organizational competitiveness and reduce organizational risks. Risks and barriers in risk-free management can be well managed through effective organizational leadership. This book will aim to bring together chapters that explore different areas of leadership.
Skin cancer shows the highest incidence worldwide, among all cancer types, and is mainly classified in melanoma and non-melanoma subtypes.
Clinical evaluation through dermatoscopy is a widely performed practice, and it is a noninvasive technique that uses magnification to allow better visualization of the structures immediately below the skin surface. This examination provides morphological criteria for distinguishing various lesions types.
Histopathology is considered the gold standard for diagnosis of skin cancer and other dermal disorders. These two exams together, as well as the location and extent of the injury will determine the choice of treatment.
Treatments such as surgical excision, cryotherapy, topical application of imiquimod cream and 5-fluorouracil cream, and radiotherapy are commonly chosen based on the depth and extension of the lesions. Limitations and side-effects of the conventional therapies motivate the development of other techniques. Photodynamic therapy (PDT) is presented as an alternative treatment for basal cell carcinoma (BCC).
PDT has proven to be effective with an excellent cosmetic outcome in the treatment of superficial BCC (sBCC), and recently published guidelines state that PDT can be an effective and reliable treatment option for the treatment of thin nodular BCC (nBCC), and actinic keratosis (AK) [1]. It is a technically simple noninvasive procedure that offers patients at least equal efficacy and a high level of satisfaction and other cosmetic outcome when compared with cryotherapy and topical treatments [2].
The term
Our group has extensive experience in clinical PDT in various areas of medicine as in gynecology [4], infectious disease [5], and in particular in dermatology [6-7], and in this chapter will be discussed the advantagens and indications of the PDT for non-melanoma skin cancer and others conditions.
Photosensitized oxidations have been of interest to chemists and biologists since Raab\'s discovery that microorganisms are killed by light in the presence of oxygen and sensitizing dyes [1].
The mechanism of action of photosensitizers is divide in two different types and generally involves direct oxidation by hydrogen peroxide (H2O2), superoxide anion radical (O2 ∙) and hydroxyl radical (∙OH) (Type I reaction) of biological targets (membranes, proteins, and DNA), as well as oxidation mediated by singlet oxygen (1O2) that is mainly formed through energy transfer from triplet states to molecular oxygen (Type II reaction) [8-10].
The generation of Reactive Oxygen Species (ROS), in both types I or II, are dependent on the uptake of a photosensitizing dye, often a haematoporphyrin derivative, by the tumor or other abnormal target tissue, the subsequent irradiation of the tumor with visible light of an appropriate wavelength, and the presence of molecular oxygen [10]. An adequate concentration of molecular oxygen is also needed for tissue damage. If any one of these components is absent, there is no photodynamic response, and the overall effectiveness therefore requires careful planning of both tissue photosensitization and light dosimetry.
PDT response is induced by more than one cellular mechanism. A photosensitiser can directly target the tumor cells, inducing necrosis or apoptosis (Figure 1) [11]. Alternatively, tumor necrosis can be induced by damaging its vasculature [12].
Treatment procedure for topical PDT. A) Skin cancer lesion; B) Cream application (MAL or ALA); C) Occlusion of the lesion; D) Illumination; E) Inflammation and tecidual necrosis; F) Curative
The photosensitizers are by definition any substance capable of making an organism, a cell or a substance photosensitive, with the photo-excitation of several types of molecules through energy transfer processes. Porphyrins, chlorines, phthalocyanines are the three main groups of studied photosensitizers (PSs). Porphyrins are the most frequently used PSs, but its systemic administration shows an important adverse factor in Dermatology. Due to the high accumulation and slow drug clearance from the skin, porphyrins lead to prolonged photosensitization of the organism after application [13]. The commercially available compounds promote a patient photosensitization that lasts for 4-6 weeks. These PDT patients must avoid sun exposure during this period, otherwise skin burns can be induced. This is the major drawback for indication of PDT in Dermatology.
The development of an ideal PDT sensitizer is still a major challenge since several characteristics must be contemplated. Main characteristics are: a) photo-excitation with red-infrared light; b) low dark toxicity; c) high stability; d) rapid clearance from the body; e) high affinity to abnormal cells (selectivity), and f) high rate of ROS production.
The main reactions observed with biological molecules are lipid peroxidation (cholesterol), cycloaddition (2 +2)-protein (reaction with tryptophan) and Diels-Alder reactions upon molecules in the genetic code (guanine). Porphyrin derivatives are indeed intersting molecules. Compounds such as porphyrins and chlorins, have the characteristics suitable for use in PDT due to the high molar extinction coefficients, high absorptivities in the region of the "therapeutic window" (600-800 nm) and with high quantum yields of singlet oxygen production.
PDT can also be performed with topical use of 5-aminolevulinic acid (5-ALA) or by its ester methyl-aminolevulinate (MAL), which are both precursors in the biosynthesis of protoporphyrin IX (PpIX), a native photosensitizing compound that accumulates in the cells. Protoporphyrin IX (PpIX) has absorption peaks at 505, 540, 580 and 630 nm.
These compounds must be stored in the form of hydrochloride (R-NH3Cl), since in its neutral form rapidly suffers degradation. Studies including a few with 5-year follow-up, have shown that ALA and MAL-PDT are comparable to other modalities in the treatment of superficial lesions considering their efficacy and with equivalent or superior cosmetic outcomes [14-15]. ALA and MAL are not photosensitizers, they are precursors of endogenous PpIX (Figure 2).
Molecular structures of the PpIX precursors.
The fundamental difference between ALA and its methyl ester (MAL) is the more hydrophobic character of the MAL. Thus, MAL can better penetrate through the cell membranes and more easily reaches the deepest epidermal layers. However, the biosynthesis of protoporphyrin IX production from MAL is slightly more time consuming because of the need of hydrolysis of this compound.
Chlorin is a photosensitizer indicated in the cases of PDT using
Recently, eight new chlorins with amphiphilic properties were synthesized from PpIX. Biological studies of some of these new chlorins indicate the great potential of these compounds as photosensitizers in PDT [17].
Distinct light sources can be used for PDT. For therapy, the tissue must be irradiated with light at appropriate wavelengths (within the absorption spectrum of porphyrins). The porphyrins exhibit a very typical absorption spectrum with the highest peak at approximately 405 nm, called the Soret-band. Other lower absorption peaks, the Q-bands, are centered at 510, 545, 580 and 630 nm. The absorption band at 630 nm is preferentially used for irradiation since light at the red spectrum results in a higher skin penetration. Lasers and incoherent light sources (lamps, light-emitting-diode – LED – lamps and, intense pulsed light – IPL) have been used. When endoscopic applications are necessary, the activating light has to be delivered through optical fibers, and laser systems are the best option for this purpose. For dermatological application, incoherent light sources are more attractive, due to the possibility of distinct emission geometries and comparable lower cost [18-20].
The therapeutic efficacy of PDT involves administration to the patient of a photosensitizer or a pro-drug, a waiting time to allow adequate concentration of the sensitizer molecules in the tumor, and irradiation of the target tissue with a proper wavelength to activate the photosensitizer generating cytotoxic products, mainly the singlet-oxygen. To trigger cell death, a minimum number of singlet-oxygen molecules have to be produced. The minimal energy dose required to achieve the irreversible tissue damage, resulting in tumor necrosis, is called the threshold dose.
The energy dose is given in Joules per centimeter square (J/cm2), that is the amount of energy delivered to the tissue per unit area. Light intensity is measured in Watts (W) and corresponds to the energy per unit of time. One W corresponds to 1 J per 1 second. Irradiance is measured in Watts per centimeter square (W/cm2), representing the light power delivered to the tissue surface [19, 21-22]. A simple relationship between light dose (D), irradiance (I) and time (t) is:
Energy doses delivered for the treatment of basal cell carcinoma and other dermal conditions are in the range of 40-150 J/cm2 and with irradiances of 40-150 mW/cm2. The PDT illumination of a BCC lesion of 2 cm of diameter, for example, may be of 8 to 20 minutes, depending on the chosen irradiation parameters.
Nonmelanoma skin cancer is the most frequent one in the world population. Currently, therapeutic options are surgical ressection, electrocoagulation, curettage, cryotherapy, immunomodulating agents, cytotoxic agents, chemotherapy, PDT, among others. PDT is a noninvasive technique with excellent cosmetic outcome, well tolerated by patients and with good healing results, when used for the initial stages of cancer lesions. Different studies show the technique effectiveness for BCC (Figure 3 and 4), presenting curative rates ranging from 52.2% to 100% [7, 23-28].
Nodular BCC before (A) and 30 days after (B) PDT, treated with MAL 20% in 2 sessions and dose of 100J/cm2
Superficial BCC before (A) and 30 days after (B) PDT, treated with MAL 20% in 2 sessions and dose of 100J/cm2
Wolf et al., (1993), in their study treated 70 different lesions – superficial BCC, actinic keratosis (AK), nodular-ulcerative BCC, squamous cell carcinoma (SCC) and melanoma – using ALA cream, with dose of 30J/cm² for superficial BCC and AK and 100 J/cm²-300 J/cm² for other lesions. Results at 12 months showed complete response for AK, 36 of 37 superficial BCC lesions showed good responses, 5 of 6 SCC, 8 cutaneous metastases of malignant melanoma were therapeutic failures and other lesions showed a partial response after treatment [23]. In the study by Calzavara (1994), which also included several lesions (AK, BCC, nodular BCC, pigmented BCC and SCC), all treated with ALA 20%, there were complete response in 100% for BCC and AK cases, decreasing to 80% in nodular lesions. Other treated lesions exhibited low curative rate when evaluated 30 days after treatment. These curative rates decreased to 86.9% in BCC and 50% in nodular BCC in the clinical follow-up done for 29 months [27]. According to the study of Souza et al., (2009), after evaluating 20 patients (showing difficulties, impediment high risk or rejection of surgical procedure) with BCC and Bowen\'s disease (BD) treated with ALA 20%, irradiated at wavelength of 630 nm and doses of 100 to 300 J\\cm², showed that, after 1 session, presented curative rates of 91.2% at three months and 57.7% at sixty months [7].
Horn et al., (2003), treated 94 patients with 108 superficial, nodular and mixed BCC lesion with difficult to treatment (resulting scars from reconstructive surgery extensive, interfering with normal function of eyelids or lips, or postoperative infections), finding complete response after 3 months in 92% of superficial BCC and 87% of nodular BCC. The cosmetic outcome was evaluated as excellent or good by investigators in 76% of the lesion after 3 months follow-up, increasing to 85% at 12 months and 94% at 24 months follow-up [29].
A recent study comparing CO2 laser ablation
Foley et al., (2009), conducted a double-blind and placebo-controlled study in primary lesion of nodular BCC (up to 5 mm in depth) in two medical centers. MAL was used at concentration of 160 mg/g cream or placebo cream, with three hours of occlusion. The light source applied was in the range of 570-670 nm, with an irradiance of 50-200 mW/cm² and dose of 75 J/cm². In total, 131 patients with 150 lesions were included in the study, 66 patients with 75 lesions were treated with MAL cream and 65 patients with 75 lesions with placebo cream. The treatment was developed in cycles. The first cycle was conducted in two sessions, with one week interval between sessions. If the response was partial (≤50% reduction in greatest diameter) after 3 months follow-up, the second cycle was initiated with two more sessions with one week interval, and monitoring the patient for six months. If the answer was not complete, the responsible medical team indicated the patient for surgical procedure. The complete response after 6 months follow-up, with MAL was of 73% (55/75 lesions) versus 27% (20/75 lesions) with placebo. The response decreases in larger lesion (≥ 10mm in diameter and ≥ 1mm of baseline depth). The cosmetic outcome of the lesions treated with MAL-PDT was good or excellent in 98% of the cases [24].
Caekelberg et al., (2009), observed the PDT result after 6 months in 90 patients with superficial BCC of approximately diameter 10 mm. The complete response rate was of 88.1% with cosmetic outcome qualified as excellent in 96.25% of patients [25].
Interesting results were achieved in the study of Surrenti et al., (2008), where they evaluated the PDT response in nodular and superficial BCC. In this study, 118 lesions were treated in 69 patients, located at the chest, face, head, neck and limbs. Superficial BCC were diagnosed in 94 lesions and 24 showed nodular BCC lesions, confirmed by histology. Complete response was obtained in 84/94 (89.4%) at superficial BCC, and in 12/23 (52.2%) at nodular BCC, when evaluated at 30 days after the second session. The cosmetic outcome was evaluated as excellent in 83% of cases and good in the remaining 17% of the cases [28].
Szeimies et al., (2008), compared PDT with surgery to treat superficial BCC between 8-20 mm size, in 196 patients with 234 lesions. The lesions treated with MAL 160 mg/g, in two sessions, showed a curative rate of 92.2% compared to 99.2% of the lesions treated with surgery, when assessed after 3 months of treatment. After 12 months, the cosmetic outcome was considered by the investigator as good or excellent in 92.8% of patients treated with PDT versus 51.2% of patients treated with surgery. The recurrence was 9.3% in comparison with 0% for lesions treated with PDT and surgery, respectively [26]. In nodular BCC treatment curative rates, after three months, of 91% with PDT versus 98% with surgery were obtained. After 12 months, 96% of lesions treated with surgery showed complete response compared to the 83% of the lesions treated with PDT. This study was performed on 97 patients with 105 lesions, all confirmed by histopathology [31].
In a recent study, (2012), was compared PDT with surgery, in 72 patients with 94 lesions superficial and nodular BCC with a maximum 3 mm thick. The patients were separated into two groups according to their choice of treatment, being 48 lesions treated with PDT and 46 with surgery. After 3 months, the curative rate was 95.83 % with PDT versus 95.65% with surgery. The recurrence rate was, after 12 months, 4.16% for PDT compared to 4.34% for surgery [32].
Basset-Seguin et al., (2008) presented results comparing PDT with cryotherapy in 118 patients. The authors used PDT protocol with MAL and two sessions separated by 7 days. The complete clinical response, after 3 months of treatment, was of 97% with cryotherapy versus 95% with PDT. Comparing the cosmetic outcome, they obtained excellent and good response in 54% versus 93% with cryotherapy and PDT, respectively [33].
Another multicenter study made by Aguilar et al., (2010), compared imiquimod and PDT with surgery in the treatment of 54 Bowen\'s disease lesions (63%) and 32 superficial BCC lesions (37%). After 24 months, the curative rate was of 97.5% for surgery, 89.5% for PDT, and 87.5% for imiquimod. The surgery cost was approximately twice the value when compared to PDT [34].
The differences between the curative results obtained in the different studies is mainly due to the distinct treament protocols: a) different lesion selection criteria (diameter, length, thickness, site, previous treatment); b) no standardization of the pre-PDT procedures (shaving, curettage, scarification); c) distinct drugs (ALA, MAL); d) different cream incubation times (2, 3 and 4 hours); e) distinct irradiation parameters; f) number of sessions; g) different treatment evaluation times (1, 3 or 6 months) and time to evaluate recurrence (6 months, 1, 3, 5 or 10 years) [35]. However, thicker lesions and nodular BCC present lower curative rates when compared to superficial BCC [26, 28, 33, 35]. Furthermore, pretreatment procedures as shaving or curettage [29], and multiple sessions [15, 36] can increase positive response to PDT [35].
PDT may present some adverse reactions such as photosensitivity, infection, erythema, edema, pain, among others [24, 37]. In topical PDT, the photosensitive drug is localized in lesion and consumed after irradiation. Reports of local photosensitivity after treatment are scarce, and when present, are present in the following 24 hours after irradiation. The systemic PDT, on the other hand, has a longer photosensitivity time [23]. Infection is a complication that almost does not occur due to the proven action of PDT for microbiological control [37]. However, some factors may predispose to this occurrence, such as, diabetes, peripheral vascular disease, and others. In a study by Wolfe et al., (2007), 700 AK lesions were treated with PDT and only 4 cases of cellulitis were reported, but easily controled by antibiotic therapy [38]. Changes in pigmentation, hyper and hypopigmentations, are reported in literature as approximately 1% of all adverse reactions [37]. The pain may be present during irradiation or within 7 days after treatment. In the study by Morton et al., (2001), only one third of patients treated had pain qualified between moderate and severe [39]. In the experiment by Ibbotson et al., (2011), during 9 years, different lesions were trated with topical PDT, 16% of patients showed severe pain and 50% moderate pain [37]. In a multicenter, randomized, controlled and open study, comparing PDT with surgery it was found that for PDT, 37/100 (37%) of patients had an adverse reaction versus 14/96 (14,6%) of patients treated with surgery. For PDT, photosensitivity reaction, which includes sensations of discomfort, burning and erythema was the most frequent, these reactions were of mild to moderate intensity and easily treated. For surgery, the more expected reaction was infection, that occured in 5 of the 14 patients and requiring the use of systemic antibiotics for two weeks [26].
PDT can be associated with other treatment techniques, such as surgery, as described by Willey et al., (2009). In this study, surgical ressection was associated with PDT with 20% ALA for recurrence prevention. The PDT protocol consisted of an hour of inoculation and illumination with a light source with wavelength at 417 nm during 1000 seconds (irradiance of 10 mW/cm²). The PDT cycles were repeated every 1-2 months for two years. In the first year after first PDT session, average reduction of lesions appearance was around 80%, reaching values of 95% reduction by the end of the second year [40].
The recurrence of BCC lesions when treated with traditional techniques has been estimated of 36% after one year of treatment, 61% after two years and 18% after 6 to 10 years of treatment [41]. For PDT, several studies have been published assessing the lesion recurrence after 1 to 5 [7, 15, 33, 42-43], 6 and 10 years of treatment [44].
In the clinical study done by Souza et al., (2009), the treated patients were monitored (or followed) for 60 months. The lesion recurrence was presented in 11/26 lesions (42.3%), the recurrence depending on the lesion types were of 2/5 for nodular BCC, 2/6 for superficial BCC and 7/15 to Bowen\'s disease [7].
According to Basset-Seguin et al., (2008), recurrence after 5 years of PDT in 103 superficial BCC, using MAL, was of 22%, all present in the first three years after treatment. This rate is comparable with the one obtained in patients treated with cryotherapy [33]. In the study by Mosterd et al., (2008), 83 nodular BCC were treated with 20% ALA-PDT and fractionated irradiation with a total dose of 150J/cm². A recurrence rate of 30.3% were obatined after 3 years. In this study, the thicknesses of 78 lesions were measured and an increased failure risk was present in thicker lesions, over 1.3 mm (42.2%), when compared to the thinner ones (15,5%) [42]. In a study by Rhodes et al., (2004), 53 nodular BCC, treated with MAL-PDT, a recurrence rate of 14% was observed after 5 years of treatment. A recurrence in 5/40 lesions treated with one PDT session and 2/9 treated with two PDT sessions, occuring especially in the first two years of treatment. When compared with surgery, the recurrence rate decreases to 4% [31]. Similar results were reported in a study of Szeimies et al., (2008), with recurrence rates for PDT of 9.3% and 0% for surgery, in a follow-up of 12 months [24].
Another study evaluating 157 BCC lesions (111 superficial BCC, 40 nodular BCC and 6 histology missing) in 90 patients treated with two sessions of MAL-PDT, recurrence rates estimated of 7% in the first 3 months, 19% in 6 months, 27% in 12 months and 31% in 24 months after treatment were obtained. When comparing recurrence rates at 12 months of nodular and superficial BCC the rates were of 28% versus 13%, respectively [43].
Christensen et al, (2009), classified 60 BCC (24 nodular BCC e 36 superficial BCC), according to size, as smaller than 1 cm, between 1-2 cm and larger than 2 cm. All lesions were curetted and DMSO was applied at the site for 5 min, then 20% ALA cream was applied and kept in position for 3 hours. PDT procedure was performed in one or two sessions. After 6 years follow up, 43/53 (81%) of lesions still showed complete response. Five patients were excluded for presenting partial response to treatment in the first three months and two patients died at the onset of follow-up period from causes unrelated to study. The recurrences were present before three years, with two thirds of these presented in the first 12 months. The average age of the patients with recurrence was of 76 y.o. for men and 77 for women. Considering lesion size, no statistical difference was observed because only one lesion measured more than 2 cm [45]. The follow up of 10 years, showed an overall curative rate of 75%, 60% for lesions treated with one session and 81% for two sessions, all recurrence cases were presented in the first three years [44].
Multiple factors have been associated with recurrence in the different studies. Few sessions are associated with high recurrence rates. One PDT session is the major factor for treatment failure [33, 44, 46]. In the study by Soler et al., (2001), 33 lesions presented recurrence, 29 of them treated with a single session and four treated with two sessions [46]. Similar data were found by Christensen et.al., (2009), where 43/53 lesions remained disease-free; 68% after one treatment session and 91% after two treatment session [45].
Size and thickness are factors that also affect lesion recurrence. The study by Mosterd et al., (2008), presented recurrence rates of 42% in the lesions with ≥ 1,3 mm thickness, and of 15.5% for lesions ≤ 1,3 mm. Horn et al., (2003), showed an increased recurrence associated with lesion size when evaluated 24 months after treatment. Lesions of 0-15 mm presented 4% recurrence, increasing to 16% in lesions of 16-30mm and greater than 30mm, 33% [29].
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Soler et al., (2001) Retrospective study [46] | \n\t\t\tMAL 160 mg/g Preparation prior PDT: Debulking procedure was performed on all nodular. | \n\t\t\tTotal: 310 lesion 131 sBCC 82 nBCC ≤ 2mm thickness 86 nBCC ≥2mm thickness | \n\t\t\t3 mo, Complete Response 91% sBCC 93% nBCC thin 86% nBCC thick 11% Recurrence at 35 mo | \n\t\t
Horn et al., (2003) Open-label study [29] | \n\t\t\tMAL 160 mg/g cream Pre-PDT procedure in nodular lesions: Shaving. | \n\t\t\tTotal:108 lesions 49 sBCC 52 nBCC 7 mixed BCC | \n\t\t\t3 mo, Complete Response 92% sBCC 87% nBCC 57% mixed BCC \n\t\t\t\t 9% Recurrence at 12 mo 18% Recurrence at 24 mo | \n\t\t
Basset –Seguin et al., (2008) Randomized, comparative, multicenter study [33] | \n\t\t\tMAL cream Preparation pre-PDT: Surface debridement | \n\t\t\tTotal 201 lesions 103 sBCC with PDT 98 sBCC with cryotherapy | \n\t\t\t3 mo, Complete response 97% PDT 95% Cryotherapy Recurrence at 5 years 22% PDT 20% Cryotherapy | \n\t\t
Szeimies et al., (2008) multicentre, randomised, controlled, open study [26] | \n\t\t\tMAL 160 mg/g cream Preparation pre-PDT: remove scales and crust of lesion surface | \n\t\t\tTotal 196 lesions 100 sBCC with PDT 96 sBCC with surgery. | \n\t\t\t3 mo Complete response 92.2% PDT 99.2% Surgery Recurrence at 12 mo 9.3% PDT 0% Surgery | \n\t\t
Christensen et al., (2009) and (2012) Prospective study study [44-45] | \n\t\t\tALA 20% DMSO 99% Preparation pre-PDT: curettage | \n\t\t\tTotal:60 lesion 24 sBCC 36 nBCC | \n\t\t\t3 mo, Complete response 92% total lesion 72 mo, Complete response 81% total lesion 120mo, Complete response 75% total lesion | \n\t\t
Lindberg-Larsen et al., (2012) Retrospective study [43] | \n\t\t\tMAL 160 mg/g Preparation pre-PDT: Superficial lesions were debrided. Nodular lesions were curetted | \n\t\t\tTotal: 157 lesion 111 sBCC 40 nBCC 6 unknown | \n\t\t\t3 mo Complete response 93% lesion Recurrence at 12 mo: nBCC 28% sBCC 13% | \n\t\t
Cosgarea et al., (2012) prospective, comparative, controlled, clinical study [32] | \n\t\t\tALA 20% cream Preparation pre-PDT: remove scales and crusts of lesion surface | \n\t\t\tTotal 94 sBCC 48 lesions with PDT 46 lesions with Surgery | \n\t\t\t3 mo Complete response 95.83% PDT 95.65% Surgery Recurrence at 12 mo 4.16% PDT 4.34% Surgery | \n\t\t
Study results of topical PDT for non melanoma skin cancer
A higher recurrence rate is also present at nodular BCC, when compared to the superficial BCC [43, 46]. Age can be a factor that increases the lesion recurrence treated with PDT, other potential factors are gender and lesion site [43].
PDT is already approved for the treatment of actinic keratosis and basal cell carcinoma. Off-label uses for PDT have been indicated for several dermatological conditions such as photo-damaged skin, scleroderma, warts, cutaneous leishmaniosis, psoriasis, cutaneous T-cell lymphoma and acne [20, 47]. Infectious disease has the potential to become one of the main indications of PDT in Dermatology. The microbiological control of bacteria, fungi and protozoa in infected lesions has been presented [48-51]. Onychomicosis is one of the new indications, where PDT presents good results even in cases where the antifungal systemic therapy failured (Paula-da-Silva, A. et al., Fast elimination of onychomycosis by hematoporphyrin derivative-photodynamic therapy. Accepted by Photodiagnosis and Photodynamic Therapy on December2012).
PDT is a noninvasive technique, with few potential adverse reactions, that presents good curative rates and excellent cosmetic outcome. It may be chosen as a first option for patients with small lesions of nonmelanoma skin cancer, especially the ones in complex sites for surgical ressection or in high risk patients.
PDT protocols and customized dosimetry for each target skin lesion still need to be defined. The development of new PDT drugs and delivery systems has the potential of increasing the curative rates of the present protocols. Instrumentation of light sources designed to adapt the emission geometry to the anatomical site characteristics is also important to improve PDT performance in cancer treatment.
The local treatment of infected lesions and cosmetics are PDT indications that have been fastly increasing. New protocols and drugs have been investigated, as well as new light devices developed, making PDT in Dermatology an exciting and growing field.
The role of fruits and vegetables in human nutrition and public health is taken into account in most nutritional recommendations. Fruit and vegetables contain an abundance of various natural compounds that have been associated with the protection and treatment of many ailments.
Terpenes are a huge and diverse category of natural compounds, obtained from a variety of plants, especially conifers, which are characteristic smelling and, in this manner, might have had a defensive function. They are the significant parts of resin and turpentine obtained from the resin. Terpenes are major biosynthetic basic compounds inside every living being. At the point when terpenes are altered chemically, i.e., by oxidation or reframing of the carbon skeleton, the subsequent mixtures are by and large alluded to as terpenoids [1].
As natural substances, terpenoids are broadly consumed in food, pharmaceuticals, and beauty care products ventures. Indeed, terpenoids are used for the counteraction and treatment of different diseases. Likewise, many investigations have additionally found that terpenoids have numerous expected applications to uncover [2]. This chapter contains updated information about the structure and diverse effects of terpenes and terpenoids.
Plant biomass is a major potential sustainable source of organic carbon. Terpenes, terpenoids and resin acids are a group of non-polar molecules and share a building block, isoprene or isoprenoid [3], as a common elementary unit (Figure 1).
Structure of isoprene unit [
Isoprene, the epitomic terpene substance, is one of the most plentifully ethereal hydrocarbon compounds on Earth attributable to the worldwide plenitude of terpenoid biosynthesis, not the other way around. Around 40% of the biogenic volatile natural compounds transmitted by plants are isoprene, and isoprene is the key hydrocarbon distinguished in human breath. Film crowds breathe out more isoprene when watching scenes of anticipation [5].
Based on ancient scientifically verified data, it is found that the expressions “isoprenoid” and “terpenoid” are applied conversely and that there is still no worldwide accord on terminology.
For instance, a few researchers have named “terpene” to allude just to hydrocarbons dependent on an indispensable number of C5 units, and “terpenoid” or “isoprenoid” to assign the entire class of compound dependent on an intrinsic number of C5 units [6].
Such compounds can be in every way called “terpenes,” and the expression “terpenoid” ought to be held for compounds, for example, the steroids, which have differing quantities of carbon molecules, however, are originated from a (C5)n structure [7]. Ruzicka considered this multitude of compounds aggregately to be “terpenic.” [8] Nes and McKean employed the expression “isoprenoid” to portray the entire group [9].
Different classes along with carbon units of terpenes and terpenoids are depicted in Figure 2.
Classification of terpenes and terpenoids.
Terpenes are significant elements of natural oils, which are secondary metabolites synthesized for battling infectious or secreted because of stress conditions. These are extricated from different fragrant plants commonly limited in mild to warm climatic regions like the Mediterranean and tropical nations where they represent a significant piece of the conventional pharmacopeia. They are ethereal, fluid, transparent, and seldom colored, lipid-dissolvable, and dissolvable in natural solvents with a by and large lower thickness than water. They can be isolated from all plant organs, for example, blossoms, buds, leaves, twigs, stems, seeds, roots, wood, fruits or bark, and are accumulated in secretory cells, holes, trenches, glandular trichomes, or epidermic cells [10].
The smallest of terpenes are monoterpenes (Figure 3). They contain the compound C10H16, come from different flowers, fruits and leaves and are known as the main component of essential oils, fragrances and many structural isomers [11]. Monoterpenes are found in natural scents for example α-pinene, which imparts scent to pine trees [12], and limonene from citrus plants [13]. One of the main purposes of monoterpenes is to attract pollinators or to serve the purpose of repelling other organisms from feeding off of plants [14].
Sub-classes of monoterpenes with structural example.
Sesquiterpenes, containing the chemical formula C15H24 (Figure 4), are much larger compounds than monoterpenes and are much more stable in comparison [15]. Sesquiterpenes are naturally occurring and found in plants, fungi, and insects and act as a defensive mechanism or attract mates with pheromones in insects [16].
Classification of sesquiterpenes with structural example.
Gossypol is a sesquiterpene that is present in cotton plants. It has anti-neoplastic properties and might hinder fertility in male people that is the reason it should be taken out from natural oils and different items before human application [17]. Avarol, a sesquiterpenoid that has been displayed to have antifungal and antimicrobial effects, is compelling against AIDS infection [18].
Diterpenes are natural substances that contain the atomic skeleton, C20H32 (Figure 5) [19]. Diterpenes have physiologically dynamic compounds, for example, plant development chemicals that manage germination, blooming, switch regenerative cycles (from abiogenetic to sexual multiplication) of plants, and vitamin A activity [20]. Cafestol and kahweol are diterpene alcohols that are found in the oil derived from coffee beans [21].
Sub-classes of diterpenes with structural example.
Triterpenes are composed of three or six isoprene units and have the chemical formula C30H48 (Figure 6) which includes steroids and sterols with squalene being the biological precursor of all Triterpenes [22]. Triterpenes are produced by animals, plants, and fungi. They play a role as precursors to steroids in animal and plant organisms, and are derived from mevalonic acid [5].
Classification of Triterpenes.
Their properties have been studied for anticancer, antioxidant, antiviral, and anti-atherosclerotic activities [23]. Although, the medicinal uses of tri-terpenes are not quite as recognized as other different types of terpenes but their uses are being continuously investigated by researchers.
Tetraterpenes are also known as carotenoids (Figure 7) that have the molecular formula C40H56 and can be in the category of terpenes because they are made from isoprene units [24]. They are found in all different types of fungi, bacteria, and plants and are mainly responsible for red, yellow, or orange fat-soluble plant and animal pigments [25]. One of the most crucial and common tetraterpenes is beta-carotene [26].
Structural example of tetraterpene.
Terpenoids, or isoprenoids, are isoprene-based compounds with major jobs in the digestion of all living beings [27]. Varieties of terpenoids are particularly high in plants where many can be viewed as secondary metabolites. Such specific plant terpenoids underlie numerous natural co-operations between plants, creatures, and microorganisms (Tables 1-4) [38], going about as allele-synthetics to repulse herbivores, tempt pollinators, or allure herbivore hunters [39]. The development of terpenoids in plants started with the enrollment of genes from primary metabolism and sped up because of the multiplication of cytochrome P450 and terpene synthase gene families in the genomes of plants [40].
Class | Plant source |
---|---|
Monoterpenes | Mentha genus, Cannabis spp. |
Sesquiterpenes | Artemisia annua L., Thapsia garganica, |
Diterpenes | Taxus brevifolia, Ricinus communis, Euphorbia peplus, |
Triterpenes | Azadirachta indica, Khaya grandifolia, Trichilia emetic, Citrus reticulate |
Tetraterpenes | Mauritia flexuosa, Brassica oleracea, Crocus sativum L. |
Class | Insect source |
---|---|
Monoterpene | |
Sesquiterpene |
Class | Fungal source |
---|---|
Monoterpenes | |
Sesquiterpenes | |
Diterpenes | |
Triterpenes |
Class | Bacterial source |
---|---|
Sesquiterpenoids | |
Diterpenoids | |
Meroterpenoids | Actinomycete isolates CNH- 099, Erythrobacter sp. strain SNB- 035, Saccharomonos pora sp. CNQ- 490 |
Terpenoid compounds partly mirrors a characteristic history set apart by herbivory stress and other particular tensions forced by creatures, bringing about a wide cluster of functionalized terpenoids in the plant realm pre-chosen for their strong organic activities towards animals [41]. This specific cycle might have been brought about by the overall closeness of protein structures and amino acid sequence among plant and creature proteins, bringing about planting auxiliary metabolites with a natural resemblance for creature proteins by ethicalness of having been delivered by plant bio-catalyst made out of similar amino acids [32].
Terpenoids are dependent on the tetracyclic 6–6–6-5 lanostane carbon skeleton structure a subsection of the terpenome known as the sterolome. The sterolome is assessed to contain about 1000 biogenic derivatives obtained from lanosterol and related particles that do fundamental organic functions across all areas of life on Earth [42].
Many plant terpenoids have been tracked down coincidentally uses in medication and the terpenoids family has been an important wellspring of clinical revelations. However, the testing system is meticulous and asset concentrated. The genuine number of plants terpenoids in nature that might be evaluated for therapeutic applications is obscure however is possibly more than 105, including more than 12,000 from the diterpenoid specifically [43]. While this number is little contrasted with current combinatorial techniques, the lead compound disclosure rate might be altogether higher for plant-based compounds. It is due to a crucial role in chemical, and metabolic processes, many are produced in limited quantities, only in response to a stimulus, or amass solely in particular tissues, requiring microbial multiplication or significant advances by plant rearing and hereditary improvement to get adequate amounts to research clinical benefits [44, 45].
Terpenoids have an expansive group of clinical activities (Figure 8) and are spread everywhere, they have been utilized in conventional medications for ancient times. Numerous compounds can be found commercially, majorly as dietary enhancements; nonetheless, some of them are enrolled as medications.
Reported and traditional therapeutic application of terpenes and terpenoids.
Human wellbeing and crop cultivation are mainly affected by insects, and trying to control these bugs the application of chemical bug sprays has become broad. Notwithstanding, this has brought about the improvement of obstruction in these living creatures, human infections, tainting of food, and contamination of the climate. Herbs and medicinal oils like terpenes and terpenoids have been displayed to have a huge potential for bug control like carvacrol, limonene, linalool, 1, 8 cineole, eugenol, and β-ionone; especially against three insects namely lice, cockroaches, and Triatominae bugs [46, 47, 48].
Antimicrobial properties or the capacity to kill or stop the development of a microorganism in terpenes are normally utilized in customary and current day medication. The accompanying plants produce terpenes that have antimicrobial potential: Pinusponderosa (Pinaceae), flavors (cumin, rosemary, thyme, caraway, clove, and sage), Cretan propolis, Helichrysumitalicum, Rosmarinus officinalis, etc. [49].
There are 52 anti-microbial terpenoids, including hydrocarbons of the oil; aromadendrene (4.4%), limonene (3.8%), α-cedrene (9.6%), β-caryophyllene (4.2%), and α-pinene (10.2%), geranyl acetic acid derivation (4.7%), 2-methylcyclohexyl pentanoate (8.3%), 2-methylcyclohexyl octanoate (4.8%), and neryl acetic acid derivation (11.5%) etc. [50, 51].
Terpenes have been shown to have a favorable anti-plasmodial activity. With the rising malarial infections and drug resistance, terpenes have gained more attention towards it through anti-plasmodial activity. Terpenes have been shown to have a favorable anti-plasmodial activity. With the rising malarial infections and drug resistance, terpenes have gained more attention towards it through anti-plasmodial activity. Different kinds of terpenes show different effects on the parasites. The most common terpenes with anti-plasmodial potential are Beta-myrcene limonene, pinene, caryophyllene, etc. Thus, terpenes could be a safer and a cost-effective alternative for malarial treatment [52, 53].
Cancer-related observational studies propose that dietary monoterpenes might be useful in the anticipation and treatment of malignant growths. Among dietary monoterpenes, D-limonene and perillyl alcohol have been displayed to have chemo-preventive and health beneficial properties against numerous human malignant growths. At present they are professed to inhibit fraction-dependent proliferation of skin, lung, mammary, liver, colon, prostate, pancreatic, and stomach carcinomas [54, 55].
Presently, the antiviral potential of terpenoids is somewhat ineffectively perceived. Consequently, there is a ton of exploration pointed towards finding agents, likewise from natural sources, which could have intense antiviral potential. The new antiviral compounds ought to explicitly restrain the virus and ought not to affect the healthy biological environment of the cell. The quest for natural antiviral moieties has paved the way for the extraction of isoborneol. Potent anti- herpes simplex virus −1 (anti-HSV-1) activities have also been reported for monoterpenes such as cineol and borneol [56, 57].
Type 2 diabetes mellitus is a chronic metabolic disorder that results from reduced first-phase insulin secretion. Stevioside is a diterpene steviol glycoside extracted from leaves of the plant Stevia rebaudiana, which possesses insulinotropic, glucagonostatic, and anti-hyperglycemic effects [58, 59].
(−)-linalool, a naturally occurring enantiomer, possesses anti-inflammatory activity. Moreover, (−)-linalool and its ester, linalyl acetate, demonstrated analgesic and edema reducing effects [60, 61, 62].
Artemisinin (sesquiterpene lactone) is secluded from
Finding a powerful boon for treating the cardiovascular problems is a pressing objective for researchers. Tanshinone IIA (TS) is a functioning moiety separated from the rhizome of Chinese home-grown medication
Tuberculosis is a very fatal disease to mankind and still the treatment regimen and new drug discovery attract the researchers to reveal a new paradigm in medical science. For the first time, diterpenoid of isosteviol, its binuclear derivatives, tri-terpenoid betulinic, oleanolic, and ursolic acids have been reported to possess anti-tubercular activity, manifested by the molecular docking method. Other natural constituents of the class are Geranylgeraniol, phytanol, escobarine A, escobarine B, furanoditerpenes, salasol A, germacrane, alantolactone, etc. [67, 68].
As of now, the clinically evident method of therapeutic activity of numerous terpenoids has not still been clarified. Besides, a relationship of “omics” technology and sub-atomic network pharmacology can be utilized to further affirm the mechanism and structural activity relationship (SAR) of terpenoids. Such study will be a promising step in the development of new medication substances thusly; the compounds with higher interest might be swiftly advanced into new medications, or structurally modified as lead compounds. It is a significant method for the innovative work and development of the medication, and it is additionally a hot spot in the subject of natural product studies. At present, reported terpenoids are about 50,000 inescapable among living beings and major fractions of them are obtained from plants. A few terpenoids are industrially notable for their dietary or therapeutic significance. The new dosage type of terpenoids might be advanced in a blend with the new techniques of pharmaceutics to expand its pharmacological activity. As more terpenoid-based clinical medications will open up, they will assume a vital part in human ailment therapy in forthcoming years. Or terpenoids might be acquainted as additives substances with wellness care items and beauty care products, which has immense market possibilities and money-related benefits. We are completely persuaded that it is the beginning stage for the fate of new green science, in light of terpenes and medicinal oils between scientists, industry, and academics.
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Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9066",title:"Wound Healing",subtitle:null,isOpenForSubmission:!1,hash:"a293ecd8c2655a402321dc30e0ffbf9a",slug:"wound-healing",bookSignature:"Muhammad Ahmad",coverURL:"https://cdn.intechopen.com/books/images_new/9066.jpg",editedByType:"Edited by",editors:[{id:"204257",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ahmad",slug:"muhammad-ahmad",fullName:"Muhammad Ahmad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7878",title:"Advances in Extracorporeal Membrane Oxygenation",subtitle:"Volume 3",isOpenForSubmission:!1,hash:"f95bf990273d08098a00f9a1c2403cbe",slug:"advances-in-extracorporeal-membrane-oxygenation-volume-3",bookSignature:"Michael S. 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Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7046",title:"Wound Healing",subtitle:"Current Perspectives",isOpenForSubmission:!1,hash:"fa7b870ad29ce1dfcf6faeafdc060309",slug:"wound-healing-current-perspectives",bookSignature:"Kamil Hakan Dogan",coverURL:"https://cdn.intechopen.com/books/images_new/7046.jpg",editedByType:"Edited by",editors:[{id:"30612",title:"Prof.",name:"Kamil Hakan",middleName:null,surname:"Dogan",slug:"kamil-hakan-dogan",fullName:"Kamil Hakan Dogan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6662",title:"Trauma Surgery",subtitle:null,isOpenForSubmission:!1,hash:"9721b9ac98bf237058cafd0a0303bdbc",slug:"trauma-surgery",bookSignature:"Ozgur Karcioglu and Hakan Topacoglu",coverURL:"https://cdn.intechopen.com/books/images_new/6662.jpg",editedByType:"Edited by",editors:[{id:"221195",title:"Prof.",name:"Ozgur",middleName:null,surname:"Karcioglu",slug:"ozgur-karcioglu",fullName:"Ozgur Karcioglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6814",title:"Current Topics in Intensive Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"5bbe8e72807443305f7cae60bfe79b9e",slug:"current-topics-in-intensive-care-medicine",bookSignature:"R?za Hakan Erbay",coverURL:"https://cdn.intechopen.com/books/images_new/6814.jpg",editedByType:"Edited by",editors:[{id:"169248",title:"Dr.",name:"Rıza Hakan",middleName:null,surname:"Erbay",slug:"riza-hakan-erbay",fullName:"Rıza Hakan Erbay"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6069",title:"Essentials of Spinal Cord Injury Medicine",subtitle:null,isOpenForSubmission:!1,hash:"f0a49e24ebfbb9ed7d02f7daab9b30f6",slug:"essentials-of-spinal-cord-injury-medicine",bookSignature:"Yannis Dionyssiotis",coverURL:"https://cdn.intechopen.com/books/images_new/6069.jpg",editedByType:"Edited by",editors:[{id:"76883",title:"PhD.",name:"Yannis",middleName:null,surname:"Dionyssiotis",slug:"yannis-dionyssiotis",fullName:"Yannis Dionyssiotis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5970",title:"Bedside Procedures",subtitle:null,isOpenForSubmission:!1,hash:"ba56d3036ac823a7155f40e4a02c030d",slug:"bedside-procedures",bookSignature:"Gabriel Cismaru",coverURL:"https://cdn.intechopen.com/books/images_new/5970.jpg",editedByType:"Edited by",editors:[{id:"191888",title:"Dr.",name:"Gabriel",middleName:null,surname:"Cismaru",slug:"gabriel-cismaru",fullName:"Gabriel Cismaru"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5756",title:"Intensive Care",subtitle:null,isOpenForSubmission:!1,hash:"c15f872f6c0158a19bf64f081fe1e854",slug:"intensive-care",bookSignature:"Nissar Shaikh",coverURL:"https://cdn.intechopen.com/books/images_new/5756.jpg",editedByType:"Edited by",editors:[{id:"107703",title:"Dr.",name:"Nissar",middleName:null,surname:"Shaikh",slug:"nissar-shaikh",fullName:"Nissar Shaikh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:14,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"50983",doi:"10.5772/63961",title:"Antimicrobial Dressings for Improving Wound Healing",slug:"antimicrobial-dressings-for-improving-wound-healing",totalDownloads:4252,totalCrossrefCites:15,totalDimensionsCites:41,abstract:"Wound healing occurs by a series of interrelated molecular events which work together to restore tissue integrity and cellular function. These physiological events occur smoothly in normal healthy individual and/or under normal conditions. However, in certain cases, these molecular events are retarded resulting in hard-to-heal or chronic wounds arising from several factors such as poor venous return, underlying physiological or metabolic conditions such as diabetes as well as external factors such as poor nutrition. In most cases, such wounds are infected and infection also presents as another complicating phenomenon which triggers inflammatory reactions, therefore delaying wound healing. There has therefore been recent interests and significant efforts in preventing and actively treating wound infections by directly targeting infection causative agents through direct application of antimicrobial agents either alone or loaded into dressings (medicated). These have the advantage of overcoming challenges such as poor circulation in diabetic and leg ulcers when administered systemically and also require lower amounts to be applied compared to that required via oral or iv administration. This chapter will review and evaluate various antimicrobial agents used to target infected wounds, the means of delivery, and current state of the art, including commercially available dressings. Data sources will include mainly peer-reviewed literature, clinical trials and reports, patents as well as government reports where available.",book:{id:"5290",slug:"wound-healing-new-insights-into-ancient-challenges",title:"Wound Healing",fullTitle:"Wound Healing - New insights into Ancient Challenges"},signatures:"Omar Sarheed, Asif Ahmed, Douha Shouqair and Joshua Boateng",authors:[{id:"183108",title:"Dr.",name:"Joshua",middleName:null,surname:"Boateng",slug:"joshua-boateng",fullName:"Joshua Boateng"},{id:"183399",title:"Dr.",name:"Omar",middleName:null,surname:"Sarheed",slug:"omar-sarheed",fullName:"Omar Sarheed"},{id:"188082",title:"Mr.",name:"Asif",middleName:null,surname:"Ahmed",slug:"asif-ahmed",fullName:"Asif Ahmed"},{id:"188083",title:"Ms.",name:"Douha",middleName:null,surname:"Shouqair",slug:"douha-shouqair",fullName:"Douha Shouqair"}]},{id:"51825",doi:"10.5772/64611",title:"Roles of Matrix Metalloproteinases in Cutaneous Wound Healing",slug:"roles-of-matrix-metalloproteinases-in-cutaneous-wound-healing",totalDownloads:3559,totalCrossrefCites:16,totalDimensionsCites:34,abstract:"Wound healing is a complex process that consists of hemostasis and inflammation, angiogenesis, re-epithelialization, and tissue remodeling. Matrix metalloproteinases (MMPs) play important roles in wound healing, and their dysregulation leads to prolonged inflammation and delayed wound healing. There are 24 MMPs in humans, and each MMP exists in three forms, of which only the active MMPs play a role in the pathology or repair of wounds. The current methodology does not distinguish between the three forms of MMPs, making it challenging to investigate the roles of MMPs in pathology and wound repair. We used a novel MMP-inhibitor-tethered affinity resin that binds only the active form of MMPs, from which we identified and quantified active MMP-8 and active MMP-9 in a murine diabetic model with delayed wound healing. We showed that up-regulation of active MMP-9 plays a detrimental role whereas active MMP-8 is involved in repairing the wound in diabetic mice. These studies identified MMP-9 as a novel target for therapeutic intervention in the treatment of chronic wounds. A selective inhibitor of MMP-9 that leaves MMP-8 unaffected would provide the most effective therapy and represents a promising strategy for therapeutic intervention in the treatment of diabetic foot ulcers.",book:{id:"5290",slug:"wound-healing-new-insights-into-ancient-challenges",title:"Wound Healing",fullTitle:"Wound Healing - New insights into Ancient Challenges"},signatures:"Trung T. Nguyen, Shahriar Mobashery and Mayland Chang",authors:[{id:"183405",title:"Prof.",name:"Mayland",middleName:null,surname:"Chang",slug:"mayland-chang",fullName:"Mayland Chang"},{id:"191152",title:"Mr.",name:"Trung",middleName:null,surname:"Nguyen",slug:"trung-nguyen",fullName:"Trung Nguyen"},{id:"191153",title:"Prof.",name:"Shahriar",middleName:null,surname:"Mobashery",slug:"shahriar-mobashery",fullName:"Shahriar Mobashery"}]},{id:"63675",doi:"10.5772/intechopen.81208",title:"Wound Healing: Contributions from Plant Secondary Metabolite Antioxidants",slug:"wound-healing-contributions-from-plant-secondary-metabolite-antioxidants",totalDownloads:1273,totalCrossrefCites:7,totalDimensionsCites:19,abstract:"Plants by their genetic makeup possess an innate ability to synthesize a wide variety of phytochemicals that help them to perform their normal physiological functions and/or to protect themselves from microbial pathogens and animal herbivores. The synthesis of these phytochemicals presents the plants their natural tendency to respond to environmental stress conditions. These phytochemicals are classified either as primary or secondary metabolites. The secondary metabolites have been identified in plants as alkaloids, terpenoids, phenolics, anthraquinones, and triterpenes. These plant-based compounds are believed to have diverse medicinal properties including antioxidant properties. Plants have therefore been a potential source of antioxidants which have received a great deal of attention since increased oxidative stress has been identified as a major causative factor in the development and progression of several life-threatening diseases, including neurodegenerative and cardiovascular diseases and wound infection. Consequently, many medicinal plants have been cited and known to effect wound healing and antioxidant properties. This chapter briefly reviews antioxidant properties of medicinal plants to highlight the important roles medicinal plants play in wound healing.",book:{id:"7046",slug:"wound-healing-current-perspectives",title:"Wound Healing",fullTitle:"Wound Healing - Current Perspectives"},signatures:"Victor Y.A. Barku",authors:[{id:"261027",title:"Prof.",name:"Victor Y. A.",middleName:null,surname:"Barku",slug:"victor-y.-a.-barku",fullName:"Victor Y. A. Barku"}]},{id:"66793",doi:"10.5772/intechopen.85020",title:"The Impact of Biofilm Formation on Wound Healing",slug:"the-impact-of-biofilm-formation-on-wound-healing",totalDownloads:1381,totalCrossrefCites:7,totalDimensionsCites:15,abstract:"Chronic wounds represent an important challenge for wound care and are universally colonized by bacteria. These bacteria can form biofilm as a survival mechanism that confers the ability to resist environmental stressors and antimicrobials due to a variety of reasons, including low metabolic activity. Additionally, the exopolymeric substance (EPS) contained in biofilm acts as a mechanical barrier to immune system cells, leading to collateral damage in the surrounding tissue as well as chronic inflammation, which eventually will delay healing of the wound. This chapter will discuss current knowledge on biofilm formation, its presence in acute and chronic wounds, how biofilm affects antibiotic resistance and tolerance, as well as the wound healing process. We will also discuss proposed methods to eliminate biofilm and improve wound healing despite its presence, including basic science and clinical studies regarding these matters.",book:{id:"7046",slug:"wound-healing-current-perspectives",title:"Wound Healing",fullTitle:"Wound Healing - Current Perspectives"},signatures:"Rafael A. Mendoza, Ji-Cheng Hsieh and Robert D. Galiano",authors:[{id:"253607",title:"M.D.",name:"Rafael",middleName:null,surname:"Mendoza",slug:"rafael-mendoza",fullName:"Rafael Mendoza"},{id:"254018",title:"Dr.",name:"Robert",middleName:null,surname:"Galiano",slug:"robert-galiano",fullName:"Robert Galiano"},{id:"271116",title:"Mr.",name:"Ji-Cheng",middleName:null,surname:"Hsieh",slug:"ji-cheng-hsieh",fullName:"Ji-Cheng Hsieh"}]},{id:"50942",doi:"10.5772/63963",title:"Cellular Therapy for Wounds: Applications of Mesenchymal Stem Cells in Wound Healing",slug:"cellular-therapy-for-wounds-applications-of-mesenchymal-stem-cells-in-wound-healing",totalDownloads:2536,totalCrossrefCites:6,totalDimensionsCites:10,abstract:"Despite progress in wound treatment including gene therapy, biological dresses and engineered skin equivalents, present treatment options for chronic wounds are restricted and not always effective. For example, inability to get consistent product from the introduced gene, biological covers may give rise to hypoxic conditions and engineered skin models are limited by their construction from substances which are hard to be degraded, and do not always result in complete replication into normal uninjured skin. A growing body of evidence suggests mesenchymal stem cells (MSCs), and their secreted growth factors and microvesicles, may potentiate the wound‐healing process and as such their addition to novel wound‐healing treatments may improve the efficacy of current therapeutic strategies. Recent studies report the ability of bone marrow‐derived MSCs (BM‐MSCs) to migrate and differentiate into skin cells in vivo.",book:{id:"5290",slug:"wound-healing-new-insights-into-ancient-challenges",title:"Wound Healing",fullTitle:"Wound Healing - New insights into Ancient Challenges"},signatures:"Moyassar B. H. Al‐Shaibani, Xiao‐nong Wang, Penny E. Lovat and\nAnne M. Dickinson",authors:[{id:"183148",title:"Dr.",name:"Moyassar",middleName:null,surname:"Al-Shaibani",slug:"moyassar-al-shaibani",fullName:"Moyassar Al-Shaibani"},{id:"183402",title:"Prof.",name:"Anne",middleName:null,surname:"Dickinson",slug:"anne-dickinson",fullName:"Anne Dickinson"},{id:"183403",title:"Prof.",name:"Penny",middleName:null,surname:"Lovat",slug:"penny-lovat",fullName:"Penny Lovat"},{id:"183404",title:"Dr.",name:"Xiao",middleName:null,surname:"Wang",slug:"xiao-wang",fullName:"Xiao Wang"}]}],mostDownloadedChaptersLast30Days:[{id:"55736",title:"Haemodynamic Monitoring in the Intensive Care Unit",slug:"haemodynamic-monitoring-in-the-intensive-care-unit",totalDownloads:3276,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Monitoring is a cognitive aid that allows clinicians to detect the nature and extent of pathology and helps assessment of response to therapy. The cardiovascular system is the most commonly monitored organ system in the critical care setting. It helps identify the presence and nature of shock and guides response to resuscitation by detection of cardiac rate and rhythm, evaluation of volume state, cardiac contractility and systemic vascular resistance. Newer technologies allow greater assessment of oxygen delivery to vulnerable tissues. We discuss the nature, history, modalities and interpretation of the most commonly available haemodynamic monitoring methods in clinical use currently.",book:{id:"5756",slug:"intensive-care",title:"Intensive Care",fullTitle:"Intensive Care"},signatures:"Mainak Majumdar",authors:[{id:"86678",title:"Dr.",name:"Mainak",middleName:null,surname:"Majumdar",slug:"mainak-majumdar",fullName:"Mainak Majumdar"}]},{id:"51825",title:"Roles of Matrix Metalloproteinases in Cutaneous Wound Healing",slug:"roles-of-matrix-metalloproteinases-in-cutaneous-wound-healing",totalDownloads:3561,totalCrossrefCites:16,totalDimensionsCites:34,abstract:"Wound healing is a complex process that consists of hemostasis and inflammation, angiogenesis, re-epithelialization, and tissue remodeling. Matrix metalloproteinases (MMPs) play important roles in wound healing, and their dysregulation leads to prolonged inflammation and delayed wound healing. There are 24 MMPs in humans, and each MMP exists in three forms, of which only the active MMPs play a role in the pathology or repair of wounds. The current methodology does not distinguish between the three forms of MMPs, making it challenging to investigate the roles of MMPs in pathology and wound repair. We used a novel MMP-inhibitor-tethered affinity resin that binds only the active form of MMPs, from which we identified and quantified active MMP-8 and active MMP-9 in a murine diabetic model with delayed wound healing. We showed that up-regulation of active MMP-9 plays a detrimental role whereas active MMP-8 is involved in repairing the wound in diabetic mice. These studies identified MMP-9 as a novel target for therapeutic intervention in the treatment of chronic wounds. A selective inhibitor of MMP-9 that leaves MMP-8 unaffected would provide the most effective therapy and represents a promising strategy for therapeutic intervention in the treatment of diabetic foot ulcers.",book:{id:"5290",slug:"wound-healing-new-insights-into-ancient-challenges",title:"Wound Healing",fullTitle:"Wound Healing - New insights into Ancient Challenges"},signatures:"Trung T. Nguyen, Shahriar Mobashery and Mayland Chang",authors:[{id:"183405",title:"Prof.",name:"Mayland",middleName:null,surname:"Chang",slug:"mayland-chang",fullName:"Mayland Chang"},{id:"191152",title:"Mr.",name:"Trung",middleName:null,surname:"Nguyen",slug:"trung-nguyen",fullName:"Trung Nguyen"},{id:"191153",title:"Prof.",name:"Shahriar",middleName:null,surname:"Mobashery",slug:"shahriar-mobashery",fullName:"Shahriar Mobashery"}]},{id:"63086",title:"Medicinal Plants in Wound Healing",slug:"medicinal-plants-in-wound-healing",totalDownloads:2804,totalCrossrefCites:6,totalDimensionsCites:10,abstract:"Wound healing process is known as interdependent cellular and biochemical stages which are in trying to improve the wound. Wound healing can be defined as stages which is done by body and delayed in wound healing increases chance of microbial infection. Improved wound healing process can be performed by shortening the time needed for healing or lowering the inappropriate happens. The drugs were locally or systemically administrated in order to help wound healing. Antibiotics, antiseptics, desloughing agents, extracts, etc. have been used in order to wound healing. Some synthetic drugs are faced with limitations because of their side effects. Plants or combinations derived from plants are needed to investigate identify and formulate for treatment and management of wound healing. There is increasing interest to use the medicinal plants in wound healing because of lower side effects and management of wounds over the years. Studies have shown that medicinal plants improve wound healing in diabetic, infected and opened wounds. The different mechanisms have been reported to improve the wound healing by medicinal plants. In this chapter, some medicinal plants and the reported mechanisms will be discussed.",book:{id:"7046",slug:"wound-healing-current-perspectives",title:"Wound Healing",fullTitle:"Wound Healing - Current Perspectives"},signatures:"Mohammad Reza Farahpour",authors:[{id:"253340",title:"Prof.",name:"Mohammadreza",middleName:null,surname:"Farahpour",slug:"mohammadreza-farahpour",fullName:"Mohammadreza Farahpour"}]},{id:"67217",title:"Nursing Implications in the ECMO Patient",slug:"nursing-implications-in-the-ecmo-patient",totalDownloads:2461,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Effective care and positive outcomes of the extracorporeal membrane oxygenation (ECMO) patient necessitate optimal interdisciplinary management from the healthcare team, including expert care from specially trained registered nurses (RNs). It is incumbent upon the RN caring for the ECMO patient to excel in both time management and assessment skills, as this population often demands care delivery at the pinnacle of intensive care unit (ICU) acuity. Astute and nuanced monitoring of neurological status, bleeding risk with potential (often massive) transfusions, poor hemodynamics, and integrity of the ECMO pump itself are only the few specialized areas of focus that must share priority with traditional nursing considerations involving the critically ill, such as prevention of pressure injuries and bloodstream infections. These high-intensity medical foci must be balanced with ethical considerations, as the ultimate goal of returning the patient to their normal life is not always possible. These demands highlight the dynamic proficiency of the RN caring for the ECMO patient. The following chapter will highlight the importance of specialized nursing care in the critically ill patient supported with ECMO.",book:{id:"7878",slug:"advances-in-extracorporeal-membrane-oxygenation-volume-3",title:"Advances in Extracorporeal Membrane Oxygenation",fullTitle:"Advances in Extracorporeal Membrane Oxygenation - Volume 3"},signatures:"Alex Botsch, Elizabeth Protain, Amanda R. Smith and Ryan Szilagyi",authors:[{id:"298623",title:"Mr.",name:"Alexander",middleName:null,surname:"Botsch",slug:"alexander-botsch",fullName:"Alexander Botsch"}]},{id:"66239",title:"Echocardiography Evaluation in ECMO Patients",slug:"echocardiography-evaluation-in-ecmo-patients",totalDownloads:2092,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Extracorporeal membrane oxygenation (ECMO) is a special form of organ support for selected cases of cardiovascular and severe respiratory failure. Echocardiography is a diagnostic and monitoring tool widely used in all aspects of ECMO support. The pathophysiology of ECMO, and its distinct effects on cardiorespiratory physiology, requires an echocardiographer with high skills to understand the interaction between the ECMO and the patient. In this chapter, we present the main application of echocardiography in ECMO patients and some general concepts on the ECMO working. ECMO, such as the standard cardiopulmonary bypass employed in cardiac surgery, V-V (veno-venous), can support the insufficient respiratory system by oxygenating and removing carbon dioxide from the blood. VA-ECMO (venous-arterial) can support haemodynamics by providing mechanical circulatory assistance. Today, ECMO can be used as bridge to decision, waiting for the development of the clinical conditions to support with other devices the evolution of cardiorespiratory failure or stop the assistance. Echocardiography (transthoracic (TTE) or transoesophageal (TOE)) can be used primarily to take decisions regarding appropriateness of ECMO support, therefore to control cannula insertion and confirm final position, to modify number and position of the cannulae in case of malfunctioning of these, and, finally, to assess clinical progress and suitability for weaning from ECMO.",book:{id:"7878",slug:"advances-in-extracorporeal-membrane-oxygenation-volume-3",title:"Advances in Extracorporeal Membrane Oxygenation",fullTitle:"Advances in Extracorporeal Membrane Oxygenation - Volume 3"},signatures:"Luigi Tritapepe, Ernesto Greco and Carlo Gaudio",authors:[{id:"284893",title:"Prof.",name:"Luigi",middleName:null,surname:"Tritapepe",slug:"luigi-tritapepe",fullName:"Luigi Tritapepe"},{id:"294005",title:"Prof.",name:"Ernesto",middleName:null,surname:"Greco",slug:"ernesto-greco",fullName:"Ernesto Greco"},{id:"294006",title:"Prof.",name:"Carlo",middleName:null,surname:"Gaudio",slug:"carlo-gaudio",fullName:"Carlo Gaudio"}]}],onlineFirstChaptersFilter:{topicId:"173",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[],lsSeriesList:[],hsSeriesList:[],sshSeriesList:[],testimonialsList:[]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"May 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:27,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:9,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",slug:"ana-isabel-flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",slug:"christian-palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",slug:"azhar-rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",slug:"sergey-sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",slug:"attilio-rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",slug:"yanfei-(jacob)-qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",slug:"arli-aditya-parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",slug:"cesar-lopez-camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",slug:"shymaa-enany",fullName:"Shymaa Enany",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRqB9QAK/Profile_Picture_1626163237970",institutionString:null,institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]},overviewPageOFChapters:{paginationCount:17,paginationItems:[{id:"81791",title:"Self-Supervised Contrastive Representation Learning in Computer Vision",doi:"10.5772/intechopen.104785",signatures:"Yalin Bastanlar and Semih Orhan",slug:"self-supervised-contrastive-representation-learning-in-computer-vision",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"79345",title:"Application of Jump Diffusion Models in Insurance Claim Estimation",doi:"10.5772/intechopen.99853",signatures:"Leonard Mushunje, Chiedza Elvina Mashiri, Edina Chandiwana and Maxwell Mashasha",slug:"application-of-jump-diffusion-models-in-insurance-claim-estimation-1",totalDownloads:2,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Data Clustering",coverURL:"https://cdn.intechopen.com/books/images_new/10820.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"81557",title:"Object Tracking Using Adapted Optical Flow",doi:"10.5772/intechopen.102863",signatures:"Ronaldo Ferreira, Joaquim José de Castro Ferreira and António José Ribeiro Neves",slug:"object-tracking-using-adapted-optical-flow",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Information Extraction and Object Tracking in Digital Video",coverURL:"https://cdn.intechopen.com/books/images_new/10652.jpg",subseries:{id:"24",title:"Computer Vision"}}},{id:"81558",title:"Thresholding Image Techniques for Plant Segmentation",doi:"10.5772/intechopen.104587",signatures:"Miguel Ángel Castillo-Martínez, Francisco Javier Gallegos-Funes, Blanca E. Carvajal-Gámez, Guillermo Urriolagoitia-Sosa and Alberto J. 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(Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}}]},{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",hash:"e7ea7e74ce7a7a8e5359629e07c68d31",volumeInSeries:2,fullTitle:"Swarm Intelligence - Recent Advances, New Perspectives and Applications",editors:[{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null}]},{type:"book",id:"7656",title:"Fuzzy Logic",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7656.jpg",slug:"fuzzy-logic",publishedDate:"February 5th 2020",editedByType:"Edited by",bookSignature:"Constantin Volosencu",hash:"54f092d4ffe0abf5e4172a80025019bc",volumeInSeries:3,fullTitle:"Fuzzy Logic",editors:[{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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